title: Poor survival with wild-type TP53 ovarian cancer?
abstract: OBJECTIVE
  The objective of this study is to investigate whether wild-type TP53 status in high-grade serous ovarian carcinoma is associated with poorer survival.
  
  
  METHODS
  Clinical and genomic data of 316 sequenced samples from The Cancer Genome Atlas (TCGA) ovarian high-grade serous carcinoma study were downloaded from TCGA data portal. Association between wild-type TP53 and survival was analyzed with Kaplan Meier method and Cox regression. The diagnosis of high-grade serous carcinomas was evaluated by reviewing pathological reports and high-resolution hematoxylin and eosin (H&E) images from frozen sections. The authenticity of wild-type TP53 in these tumor samples was assessed by analyzing SNP array data with ASCAT algorithm, reverse phase protein array (RPPA) data and RNAseq data.
  
  
  RESULTS
  Fifteen patients with high grade serous ovarian carcinomas were identified to have wild-type TP53, which had significantly shorter survival and higher chemoresistance than those with mutated TP53. The authenticity of wild-type TP53 status in these fifteen patients was supported by SNP array, RPPA, and RNAseq data. Except four cases with mixed histology, the classification as high grade serous carcinomas was supported by pathological reports and H&E images. Using RNAseq data, it was found that EDA2R gene, a direct target of wild-type TP53, was highly up-regulated in samples with wild-type TP53 in comparison to samples with either nonsense or missense TP53 mutations.
  
  
  CONCLUSIONS
  Although patients with wild-type TP53 ovarian cancer were rare in the TCGA high grade ovarian serous carcinomas cohort, these patients appeared to have a poorer survival and were more chemoresistant than those with mutated TP53. Differentially expressed genes in these TP53 wild-type tumors may provide insight in the molecular mechanism in chemotherapy resistance.
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. kkwong@mdanderson.org
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
authors.forename: Daisy I
authors.initials: DI
authors.lastname: Izaguirre
authors.forename: Suet-Yan
authors.initials: SY
authors.lastname: Kwan
authors.forename: Erin R
authors.initials: ER
authors.lastname: King
authors.forename: Michael T
authors.initials: MT
authors.lastname: Deavers
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Mok
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
mesh_terms: D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D040081:Protein Array Analysis; D017423:Sequence Analysis, RNA; D015854:Up-Regulation; D053340:Xedar Receptor / Q000235:genetics*
chemical_list: C506011:EDA2R protein, human; D053340:Xedar Receptor
keywords: Collagen VI; EDA2R; Ovarian cancer; Survival statistics; Wild-type p53; p53 mutation